Ultragenyx Pharmaceutical Inc. announced positive longer-term safety and efficacy data from the first three cohorts of the ongoing Phase 1/2 studies of DTX401, an investigational adeno-associated virus (AAV) gene therapy for Glycogen Storage Disease Type Ia (GSDIa), and DTX301, an AAV gene therapy for ornithine transcarbamylase (OTC) deficiency. In addition, dosing is nearing completion for the prophylactic steroid cohorts in both studies. Discussions with regulatory agencies continue to progress for both programs, and Ultragenyx expects to initiate Phase 3 studies for DTX401 in the first half of 2021 and for DTX301 in the second half of 2021. The company also plans to start a seamless single-protocol Phase 1/2/3 study for UX701, an AAV gene therapy for Wilson disease. Phase 1/2 data update: All patients (n=9) responding and demonstrating continued improvement of glucose control while reducing or eliminating cornstarch therap. All nine patients continue to demonstrate improved glucose control while tapering or discontinuing oral glucose replacement with cornstarch and improvements in energy metabolism pathways over the long term. Patients continue to taper the amount and frequency of cornstarch dosing with progress in eliminating overnight and daytime cornstarch doses. At the primary evaluation timepoint at Week 52, the overall mean reduction in cornstarch was 77% across all three cohorts, including two patients in Cohort 3 showing a reduction of greater than 75%. Longer term follow-up for more than two years for the three patients in Cohort 1 have shown sustained and continued cornstarch reductions with a mean reduction of 91% through weeks 104 and 120. Two patients (one each from Cohort 1 and 3) are completely off cornstarch therapy at weeks 127 and 60, respectively. Data collected from continuous glucose monitoring (CGM) implemented in Cohort 3 indicate that glycemic control was maintained and even improved despite the reductions in cornstarch dependence. Through Week 48, these patients had decreased cornstarch use by between 30% and 92%. Even with these substantial cornstarch reductions, the patients had a mean 10% increase in the percent of time spent in euglycemia, defined by blood glucose levels in the normal range of 60 to 120 mg/dL. Additionally, these reductions in cornstarch dosing have had an impact on energy metabolism and body weight. Seven of nine treated patients had decreases of 5% (5.6 kg) to 21% (10.5 kg) in bodyweight following DTX401 treatment, with a mean decrease of 12% from the mean baseline weight of 82.8 kg in these seven patients. The notable weight loss is attributed to improved glycemic control and potentially increased physical activity reported by patients. Interviews with patients following their Week 24 and/or Week 52 visits provide support for the study results seen to date. Patients reported improvements in both their physical and mental health. This includes increased energy and strength, supporting normalization of daily activities and weight loss, as well as greater mental acuity and reduced stress, with the latter in part noted as related to diminished fears of missing a cornstarch dose. No negative patient feedback has been received to date on their experiences with DTX401. The safety profile of DTX401 remains favorable; there have been no infusion-related adverse events and no treatment-related serious adverse events reported. All adverse events have been Grade 1 or 2. All three patients in a fourth and final Phase 1/2 cohort, which utilizes prophylactic steroids, have been dosed at the same dose as Cohorts 2 and 3. There have been no safety issues through up to 11 weeks post-dosing, and all three patients are doing well and have demonstrated early reduction in daily cornstarch intake.